Being involved in combat is a horrific experience that substantially increases the risk of developing posttraumatic stress disorder (PTSD). Although several effective treatments have been identified for PTSD a substantial number of patients (up to 50%) continue to experience symptoms. In fact, combat related PTSD is even less responsive to existing treatments than PTSD caused by other traumatic experiences. In short, the treatment for chronic PTSD is inadequate. The field of neuroscience has revealed that patients with PTSD demonstrate altered functioning within, and interactions between, several brain regions; findings that are consistent with animal models of chronic stress. Despite this evidence, existing treatments are generally not designed using this neuroanatomical knowledge. The central premise of the proposed study is that neuroscientifically-based information can be used to develop more precise and effective treatments. High definition transcranial direct current stimulation (HD-tDCS) will be used to correct the dysfunctional brain regions (and communication between these regions), with the expectation that this modulation will result in symptom improvement. The primary goals of the proposed R21/R33 are to verify the maladaptive brain networks and then establish evidence that HD-tDCS modulates these networks (R21 phase). Latter studies (R33 phase) will examine dose-response relationships and synergistic effects of HD-tDCS and existing treatments. In both phases, outcome will be assessed using a multi-method approach that includes functional connectivity using resting-state functional magnetic resonance imaging data, neuropsychological tests, and self-report measures of emotional functioning. The combined results will provide vital methodological, mechanistic, and practical information necessary for a formal clinical trial of tDCS in PTSD. Ultimately, the proposed approach could reinforce a fundamental shift in the development and implementation of treatments for mental illnesses that share common core features, which is consistent with the NIMH's Strategic Plans to classify and treat mental disorders using behavioral dimensions and neurobiological measures.